The main olfactory and vomeronasal systems are two of several nasal chemoreceptive systems present in terrestrial vertebrates. They are major sources of direct exteroceptive information to the limbic system and have been implicated in a number of species-typical behaviors. A major question that has not yet been elucidated is the relationship between the vomeronasal and main olfactory systems in guiding behavior. We are using snakes to study interactions between the vomeronasal and olfactory systems because snakes have extraordinarily well developed vomeronasal systems that are of critical importance in naturally occurring behaviors, such as courtship, prey discrimination and aggregation. We have isolated and purified proteins from earthworms, a major part of the natural diet of garter snakes, that are detected by the vomeronasal system and propose to continue these studies to better understand the molecular and cellular basis of vomeronasal stimulus transduction. We are analyzing prey substances in an integrated fashion, isolating, purifying and characterizing chemoattractants from earthworms, studying their ability to bind to vomeronasal epithelial membranes and testing their potency behaviorally and electrophysiologically. In contrast to the volatile stimuli of the olfactory system, purified vomeronasal stimulants are relatively large, nonvolatile molecules, and animals must actively introduce them into the vomeronasal organ. We propose to study the route of delivery of odorants into the vomeronasal organ, the role of the olfactory system in activating the vomeronasal delivery mechanism, and the relative role of olfactory and vomeronasal system in guiding behaviors that lead to the detection of prey chemicals, both volatile and nonvolatile.